Evaluation of a Modified APTT-Based Method for Determination of APC Resistance in Plasma from Patients on Heparin or Oral Anticoagulant Therapy

Hall, Christina; Andersson, Nils-Erik; Andras, Maria T.; Zetterberg, U.; Rosén, S.

doi:10.1016/s0049-3848(98)00006-1

Cited by 7 publications

(7 citation statements)

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“…The tests belonging to this third class are highly specific and sensitive and they include dilution of the patient's plasma in an FV-deficient plasma. [113][114][115][116] Because of dilution of interfering factors in a uniform FV-deficient plasma, interference is minimized and/or masked by the standardized levels of factors in the deficient plasma. Most of these tests, reviewed by Bertina,117 are clotting-based tests, but a spectrophotometric method has also been reported.…”

Section: Laboratory Assays For the Detection Of Apc Resistancementioning

confidence: 99%

Congenital and Acquired Activated Protein C Resistance

Nicolaes¹,

Dahlbäck²

2003

Seminars in Vascular Medicine

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Resistance to the anticoagulant action of activated protein C, APC resistance, is a highly prevalent risk factor for venous thrombosis among individuals of Caucasian origin. In most cases, APC resistance is associated with a single missense mutation in the gene for coagulation factor V (FV (Leiden)), which predicts the replacement of Arg (506) with a Gln at one of the cleavage sites for APC in factor V. Factor V is a Janus-faced protein with dual functions, serving as an essential nonenzymatic cofactor in both pro- and anticoagulant pathways. Procoagulant factor Va, generated after proteolysis by thrombin or factor Xa, is a cofactor to factor Xa in the activation of prothrombin, whereas anticoagulant factor V, generated after proteolysis by APC, functions as a cofactor in the APC-mediated degradation of FVIIIa. The FV (Leiden) mutation affects the anticoagulant response to APC at two distinct levels of the coagulation pathway, as it impairs degradation of both activated factor V and activated factor VIII, the latter effect inasmuch as FVLeiden is a poor APC cofactor. Several other genetic traits, some of them quite common, are known to affect the anticoagulant response to APC, but none of them cause the same severe APC-resistance phenotype as FV (Leiden) and their importance as risk factors for thrombosis is unclear. A poor APC response may also result from acquired conditions, some of which are clearly involved in the pathogenesis of venous thrombosis. Venous thrombosis is a typical multifactorial disease, the pathogenesis of which involves multiple gene-gene and gene-environment interactions. In many patients with severe thrombophilia, APC resistance is found as a contributing risk factor.

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Section: Laboratory Assays For the Detection Of Apc Resistancementioning

confidence: 99%

Congenital and Acquired Activated Protein C Resistance

Nicolaes¹,

Dahlbäck²

2003

Seminars in Vascular Medicine

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“…Heterozygosity for FVL confers a 3-to 7-fold increase in the risk of thromboembolic events, whereas homozygosity is associated with an 80-fold increase. 8,9 FVL affects approximately 5% of the white population and is responsible for more than 95% of cases of APCR. 8,10,11 Activated protein C is a plasma anticoagulant that cleaves factor Va at several conserved arginine residues.…”

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confidence: 99%

“…15,16 The dilution with factor V-deficient plasma also rendered the test suitable for use in patients on heparin (with the addition of a heparin neutralizer) and vitamin K antagonists (eg, warfarin), as well as in patients with acute thromboembolic events. 9,11,14,16 The sensitivity and specificity of the APCR test in those patients approaches 100%. 11,[15][16][17] However, data concerning its sensitivity in patients taking factor Xa inhibitors, such as apixaban, are still scarce.…”

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confidence: 99%

Apixaban Does Not Interfere With Protein S or Activated Protein C Resistance (Factor V Leiden) Testing Using aPTT-Based Methods

Maryamchik

Cott

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Apixaban causes a false increase in activated protein C resistance (APCR) ratios and possibly protein S activity. Objective.— To investigate whether this increase can mask a diagnosis of factor V Leiden (FVL) or protein S deficiency in an actual population of patients undergoing apixaban treatment and hypercoagulation testing. Design.— During a 4.5-year period involving 58 patients, we compared the following 4 groups: heterozygous for FVL (FVL-HET)/taking apixaban, wild-type/taking apixaban, heterozygous for FVL/no apixaban, and normal APCR/no apixaban. Patients taking apixaban were also tested for protein S functional activity and free antigen (n = 40). Results.— FVL-HET patients taking apixaban had lower APCR ratios than wild-type patients ( P < .001). Activated protein C resistance in FVL-HET patients taking apixaban fell more than 3 SD below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite apixaban. In contrast to rivaroxaban, apixaban did not interfere with the assessment of protein S activity (mean activity 93.9 IU/dL, free antigen 93.1 IU/dL, P = .39). A total 3 of 40 patients (8%) had low free protein S antigen (30, 55, and 57 IU/dL), with correspondingly similar activity results (27, 59, and 52 IU/dL, respectively). Apixaban did not cause a missed diagnosis of protein S deficiency. Conclusions.— Despite apixaban treatment, APCR testing can distinguish FVL-HET from healthy patients, rendering indiscriminate FVL DNA testing of all patients on apixaban unnecessary. Apixaban did not affect protein S activity.

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“…12,13 It also rendered the test suitable for use in patients on heparin and vitamin K antagonists (eg, warfarin), as well as in patients with acute thromboembolic events. 6,8,11,14 The sensitivity and specificity of the APCR test in those patients approached 100%. 8,12,13,15 However, data concerning its sensitivity in patients taking Xa inhibitors, such as rivaroxaban, are still scarce.…”

mentioning

confidence: 98%

“…Heterozygosity for FVL confers a 3-to 7-fold increase in the risk of thromboembolic events, whereas homozygosity is associated with an 80-fold increase. 5,6 FVL affects about 5% of the white population and is responsible for more than 95% of cases of APCR. 5,7,8 Activated protein C is an intrinsic plasma anticoagulant that cleaves factor Va at several conserved arginine residues.…”

mentioning

confidence: 99%